Evidence map›Paper›PMID 35333737›Full record

ArticleEuropean journal of endocrinology2022

Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma.

Steven G Waguespack, Alexander Drilon, Jessica J Lin, Marcia S Brose, Ray McDermott, Mohammed Almubarak, Jessica Bauman, Michela Casanova, Anuradha Krishnamurthy, Shivaani Kummar and 10 more

3 registry-linked trialsOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of endocrinology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 90 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 5 pooled it
17.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02122913 phase1completednot on this map

A Phase 1 Study of the Oral TRK Inhibitor Larotrectinib in Adult Patients With Solid Tumors

TypeinterventionalSponsorBayerRan2014 to 2021Enrolled75ConditionsSolid Tumors Harboring NTRK FusionArmsLarotrectinib (Vitrakvi, BAY2757556)
NCT02576431 phase2completednot on this map

A Study to Learn How Well the Drug Larotrectinib Works in Adults With Different Solid Cancers With a Change in the Genes Called NTRK Fusion

TypeinterventionalSponsorBayerRan2015 to 2025Enrolled215ConditionsSolid Tumors Harboring NTRK FusionArmsBAY2757556 (Larotrectinib, Vitrakvi)
NCT02637687 phase1 / phase2active not recruitingnot on this map

A Phase 1/2 Study of the Oral TRK Inhibitor Larotrectinib in Pediatric Patients With Advanced Solid or Primary Central Nervous System Tumors

TypeinterventionalSponsorBayerRan2015 to 2026Enrolled154ConditionsSolid Tumors Harboring NTRK FusionArmsLarotrectinib (Vitrakvi, BAY2757556)
3 · Its place in the literature

Who cites it

90 citing papers in PubMed, 5 syntheses or guidelines pooled it, 134 citations in OpenAlex.

  1. Guideline
  2. Guideline
  3. Guideline
  4. Guideline
  5. SEOM-GETNE-TTCC Clinical guideline thyroid cancer (2023).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Guideline
  6. Trial
  7. Trial
  8. Trial
  9. Molecular and clinicopathological characteristics ofHistology and histopathology · 2026
    Review
  10. Article
  11. Review
  12. Article
  13. Genomics and Multi-Omics to Guide Clinical Management in Thyroid Cancer.International journal of molecular sciences · 2026
    Review
  14. Article
  15. Review
  16. Thyroid Cancer: Epidemiology, Diagnosis, and Treatment.Deutsches Arzteblatt international · 2026
    Review
  17. Article
  18. Review
  19. Article
  20. Article

30 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 16 institutions in 6 countries.

Steven G WaguespackThe University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID 0000-0003-0280-0100
Alexander DrilonMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Jessica J LinMassachusetts General Hospital, Boston, Massachusetts, USA.
Marcia S BroseSidney Kimmel Cancer Center of Jefferson University Health, Philadelphia, Pennsylvania, USA.
Ray McDermottSt Vincent's University Hospital and Cancer Trials Ireland, Dublin, Ireland.
Mohammed AlmubarakWest Virginia University, Morgantown, West Virginia, USA.
Jessica BaumanFox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Michela CasanovaPaediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Anuradha KrishnamurthyUPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Shivaani KummarStanford Cancer Center, Stanford University, Palo Alto, California, USA.
Serge LeyvrazCharité - Universitätsmedizin Berlin, Berlin, Germany.
Do-Youn OhSeoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea.
Keunchil ParkSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Davendra SohalUniversity of Cincinnati, Cincinnati, Ohio, USA.
Eric ShermanMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Ricarda NorenbergChrestos Concept GmbH & Co. KG, Essen, Germany.
Josh D SilvertownBayer HealthCare Pharmaceuticals, Inc., Toronto, Canada.
Nicoletta BregaBayer S.p.A, Milan, Italy.
David S HongThe University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Maria E CabanillasThe University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
The University of Texas MD Anderson Cancer Center · USMemorial Sloan Kettering Cancer Center · USBayer (Canada) · CABayer (Italy) · ITCancer Trials Ireland · IECharité - Universitätsmedizin Berlin · DEFondazione IRCCS Istituto Nazionale dei Tumori · ITFox Chase Cancer Center · USHarvard University · USSamsung Medical Center · KRSeoul National University Hospital · KRSidney Kimmel Cancer Center · USStanford University · USUniversity of Cincinnati · USUPMC Hillman Cancer Center · USWest Virginia University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Objective: Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with demonstrated efficacy across various TRK fusion-positive solid tumours. We assessed the efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma (TC). Methods: We pooled data from three phase I/II larotrectinib clinical trials (NCT02576431, NCT02122913, and NCT02637687). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Data cut-off: July 2020. Results: Twenty-nine patients (median age: 60; range: 6-80) with TRK fusion-positive TC were treated. Tumour histology was papillary (PTC) in 20 (69%) patients, follicular (FTC) in 2 (7%), and anaplastic (ATC) in 7 (24%) patients. Among 28 evaluable patients, ORR was 71% (95% CI: 51-87); best responses were complete response in 2 (7%) patients, partial response in 18 (64%), stable disease in 4 (14%), progressive disease in 3 (11%), and undetermined in 1 (4%) due to clinical progression prior to the first post-baseline assessment. ORR was 86% (95% CI: 64-97) for PTC/FTC and 29% (95% CI 4-71) for ATC. Median time to response was 1.87 months (range 1.64-3.68). The 24-month DoR, PFS, and OS rates were 81, 69, and 76%, respectively. Treatment-related adverse events were mainly grades 1-2. Conclusion: In TRK fusion-positive TC, larotrectinib demonstrates rapid and durable disease control and a favourable safety profile in patients with advanced disease requiring systemic therapy. Significance statement: NTRK gene fusions are known oncogenic drivers and have been identified in various histologies of thyroid carcinoma, most commonly in papillary thyroid carcinoma. This is the first publication specifically studying a TRK inhibitor in a cohort of TRK fusion-positive thyroid carcinoma patients. In the current study, the highly selective TRK inhibitor larotrectinib showed durable antitumour efficacy and a favourable safety profile in patients with TRK fusion-positive thyroid carcinoma. Our findings show that patients with advanced non-medullary thyroid carcinoma who may require systemic therapy could be considered for testing for gene fusions by next-generation sequencing.

Indexed as

PyrazolesPyrimidinesThyroid NeoplasmsAdolescentAdultAgedAged, 80 and overAntineoplastic AgentsChildClinical Trials, Phase I as TopicClinical Trials, Phase II as TopicHumansMiddle AgedProtein Kinase InhibitorsYoung AdultAntineoplastic AgentslarotrectinibProtein Kinase InhibitorsPyrazolesPyrimidines

Identifiers

PMID35333737
PMCPMC9066591
OpenAlexW4220804542

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.